Arrangement for preparing natural tissue for implantation

ABSTRACT

An arrangement for preparing natural tissue in the form of a heart valve, vessel or the like for implantation in which tanning fluid under pressure is applied to a portion of the tissue so as to cause said tissue to assume substantially its natural configuration, while additional tanning fluid is applied to the remainder of the tissue, said tanning fluid being so applied for a time sufficient to cause the tissue to become fixed, and, for vessels or the like, a guide may engage the tissue during fixation, whereby said tissue maintains substantially the configuration of the guide.

REFERENCE TO RELATED APPLICATIONS

This is a continuation of patent application Ser. No. 490,686, filedJuly 22, 1974, now abandoned which is a continuation-in-part of ourapplication Ser. No. 324,217 filed Jan. 16, 1973, now abandoned, whichwas a continuation of patent application Ser. No. 28,630, filed Apr. 15,1970, now abandoned.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to the preparation of natural tissue forimplantation.

2. Description of Prior Art

Natural aortic valves taken from animals or humans have been used for anumber of years for allo and xenograft replacement of diseased valves.This has experienced only limited success, however, as in a largeproportion of cases the replacement valves develop leakage. Theincidence of incompetency has run from 40% to 80%. This occurs primarilybecause the valve is a very flexible and elastic structure which doesnot maintain its normal physiologic state when removed from the donorheart. This readily distortable element must then be matched with theflexible structure of the patient's heart, which also is not in itsnormal physiologic state when prepared for the valve replacement. Withdistortion of the flexible valve being unavoidable, and with no twovalves being the same, it becomes virtually impossible to affix thevalve to a stent or the patient's annulus at the proper location tomaintain the valve's natural configuration. Consequently, undesirablestresses are introduced into the valve. This may result in immediateincompetence of the valve. Even where this does not prevent competenceinitially, the existence of the stresses in the valve over a period oftime frequently causes premature failure.

If an appropriate tanning fluid is applied to a natural heart valve, itstissue becomes fixed so that it loses its characteristic of extremeflexibility and elasticity. As a result, in order to assure retention ofapproximately normal geometry, the cusps of the allo and xenograftvalves have been packed with cotton, and the valves then have been fixedby tanning. This, however, has not solved the problem of valve failurebecause it never has been possible to impart exactly its naturalconfiguration to a valve by packing it with cotton or similar material.Consequently, there are inevitably variations from the normal valveshape, and these differences become fixed in the valve by the tanningoperation. These shape variations introduce stresses in the valve, whichmay cause it to fail subsequently.

Another problem encountered from such tanning of the valve is thatshrinkage occurs as a result of this procedure. The amount of shrinkageis not the same in different valves, so that there is no way ofpredicting how much shrinkage will take place. Later, when the valve isexposed to biologic fluid after it has been implanted, it experiencessome re-expansion. Again, this is an unknown amount. These factorscontribute to the difficulty in properly mounting the valve and make theintroduction of undesirable stresses practically unavoidable.

Similar problems have been encountered with vessels which also have beenprepared for implantation by fixation with a tanning fluid. Problemshave included inadequate penetration of the fixative, a lack ofuniformity of fixation and insufficient tensile strength in the preparedvessels.

SUMMARY OF THE INVENTION

The present invention overcomes the difficulties previously encounteredwith natural valves, vessels and the like. It permits a natural heartvalve to be fixed in its natural state so that it will retain its shapeand can be readily and correctly mounted on a stent or affixed directlyto the annulus of the heart of the patient. By this procedure, the valveis subjected to fluid pressure and at the same time fixed by exposure toa tanning fluid. It has been found that, when fluid pressure is appliedto a valve after removal from the heart, the valve will be given itsnatural shape. Therefore, when fixed in a pressurized condition, thevalve will retain its normal architecture, allowing proper mounting tobe achieved. Similarly, vessels are subjects to pressure while beingfixed with comparable improved results.

The valve may be pressurized by introducing the tanning fluid into itwhile subjecting the exterior of the valve to a bath of the same tanningfluid. In accomplishing this, the valve and associated ascending aortaare excised from the donor heart and attached to a stopper which has anopening through it. The tanning fluid is introduced through this openinginto the interior of the valve, and a normal physiologic pressure isapplied. This may be accomplished accurately by providing a source ofthe tanning fluid at a predetermined height with respect to the valve,so that the pressure head on the valve is at the correct value. After anappropriate period in the tanning solution, the valve is fixed in itsnatural contour and, upon removal, will retain this shape. Then, upontrimming, it is ready for mounting on a stent or for attachment to theheart of the patient. The prepared valve also may be stored frozen forfuture use or stored in the solution.

When fixed under pressure in this manner, the valve does not shrinkduring the tanning process, nor does undesirable expansion occursubsequently when the valve is subjected to the biologic fluid. Thetanning process takes place more rapidly when the tanning solution isunder pressure. Also, when tanned under pressure, the tensile strengthof the tissue of the valve becomes increased. Improved results areobtained additionally because, when subjected to the pressure of thetanning fluid, valves that inherently will leak may be detected throughthe loss of fluid through the valve. These may be discarded to that onlyproperly functioning valves will be retained for subsequentimplantation.

In preparing a vessel, the collaterals and one end are ligated, and theother end is attached to a source of pressurized tanning fluid. Whilethe interior of the vessel is subjected to the pressurized tanningfluid, the exterior is submersed in a bath of the tanning fluid. Thenatural overall contour of the vessel may be maintained as it is fixedby engaging it with a guide having the same general shape as the naturalvessel contour. The guide also may impart a different contour to thevessel so that special shapes can be produced. The guide may be a rodreceived within the vessel or a tube surrounding the vessel.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a longitudinal sectional view of a valve structure attached toa device for applying pressurized tanning fluid and after being fixed bythe tanning fluid;

FIG. 2 is an elevational view, partially in section, illustrating anarrangement for treating a number of valves;

FIG. 3 is a top plan view showing the manifolding arrangement fordistributing the tanning fluid;

FIG. 4 is a sectional view taken along line 4--4 of FIG. 1;

FIG. 5 is a view similar to FIG. 4 but illustrating the appearance of avalve in the absence of treatment in accordance with this invention;

FIG. 6 is a side elevational view, partially in section, illustratingthe arrangement for fixing vessels for implantation, utilizing straightrods for maintaining the configurations of the vessels;

FIG. 7 is an enlarged fragmentary view of a portion of the arrangementof FIG. 6, the vessel being shown internally pressurized;

FIG. 8 is a view similar to FIG. 7 but of a vessel receiving a curvedrod as a guide member, with the vessel shown pressurized; and

FIG. 9 is a view similar to FIGS. 7 and 8, but with a tube used to guidethe vessel, and with the vessel shown unpressurized.

DESCRIPTION OF THE PREFERRED EMBODIMENT

In preparation for a transplant, an aortic valve 10 is excised alongwith the ascending aorta 11 and extraneous tissue removed. This includesremoval of the aorta above the sinus of the Valsalva, the annulus andsubvalvular structure. The coronary arteries 12 are ligated by sutures13. The aorta 11 then is extended around a rubber stopper 15, which hasa central axially extending opening 16 through it. The stopper 15,therefore, is positioned in the aorta 11 above the valve 10, between thevalve and the arch of the aorta. A suture 17 is wrapped around theexterior to affix the aorta to the stopper 15. The result is theformation of a chamber 19 within the valve structure, closed at itslower end by the cusps 20 of the valve. Access to the upper portion ofthe chamber 19 is provided by the opening 16 through the stopper 15.This allows pressurized tanning fluid to be introduced into the chamber19 to fix the valve 10 in its natural configuration.

In order to pressurize the valve, the arrangement shown in FIGS. 2 and 3may be employed, which provides a means for treating a number of valvessimultaneously. This system includes an open-topped tank 22 from thebottom of which extends a line 23 to a pump 24. The latter, through aconduit 25, connects to a reservoir 26 that is located above the tank22. A filter 27 in the line 25 will remove any impurities in fluidconducted through the line 25 to the reservoir 26. Extending downwardlyfrom the reservoir 26 is a line 28, the lower end of which connects to amain manifold 29. A shutoff valve 30 may be included in the line 28.Additional and smaller manifolds 31 extend outwardly from the mainmanifold 29, each of these being provided with a plurality of downwardlyextending stems 32. The openings 16 of stoppers 15 to which valveelements have been attached receive the open lower ends of the stems 32.This positions the valve structures 10 within the tank 22.

A suitable tanning fluid 33, such as formaldehyde, glutaraldehyde orother aldehyde, is introduced into the tank 22 and the reservoir 26. Thefluid 33 in the tank 22 covers the exteriors of the valve structures 10.This causes the upstream ends of the valves 10 to be submerged in thetanning fluid 33.

The fluid 33 from the reservoir 26 fills the interior chambers 19 of thevalves 10, where it is retained by the cusps 20. Because the reservoir26 is elevated with respect to the location of the valves 10, a staticpressure head is developed which causes the tanning fluid in thechambers 19 to exert pressure against each of the valves 10. This fluidpressure applied from the proximal aorta, being thus on the downstreamside of the valve 10, inflates the valve and causes the valve to assumeits natural contour. The maximum elevation of the fluid 33 in thereservoir 26 is kept at a height to produce a pressure head such thatthe valves will be pressurized within the physiologic range. This isfrom 80 to 120 mm Hg, with 80 mm Hg being used most frequently as thepressurizing value. The pressurization is controlled accurately andchanged as needed by selecting an appropriate elevation of the reservoir26 over the tank 22 to result in a desired pressure head. This pressureis maintained within the chambers 19 of the valve structures for aperiod sufficient to attain a fixation of the tissue of the valves. In a4% formaldehyde solution or a 0.2% glutaraldehyde solution, this willoccur in around 72 hours.

After being maintained under fluid pressure in the presence of thetanning fluid, the valve is removed and then may be handled withoutdisturbing its natural geometry. It is then ready for mounting on astent or for being affixed in the annulus of the heart of a patient. Thenatural shape of the valve may be maintained without difficulty as it ismounted, because any distortion is visually apparent. The valve willkeep its shape when prepared in this manner, exhibiting neithershrinkage from the preparation nor expansion from subsequent contactwith biologic fluid. The chance of incompetence, even after a prolongedperiod of subsequent use, is greatly reduced. The tissue of the valveachieves a higher tensile strength as a result of the tanning underpressure for greater life and assured performance. Furthermore, theprocess serves for quality control as valves exhibiting excess leakagecan be detected and discarded. In the event that leakage past the cusps20 of the valves 10 raises the level of the fluid 33 in the tank 22 toohigh, the excess is returned to the reservoir 26 by the pump 24.

In appearance, the prepared valve will resemble the illustration of FIG.4 with a generally regular contour and coaptation of the cusps 20. Thecusps are closed as in diastole, and the valve is in its normalphysiologic state. Without the treatment in accordance with thisinvention, the valve may appear generally as shown in FIG. 5, with anuneven contour and the potential of leakage through the cusps.

The process of this invention as used in preparing arteries and veinsfor implantation may be seen in FIGS. 6 and 7. Here, one end of a vessel35 is fitted over the downwardly extending stem 36 of a fluid manifold37, held to it by means of sutures 38. The manifold 37 may be generallysimilar to the manifold 31 described above. The vessel 35 is receivedwithin a shallow tank 39 containing the tanning fluid 33. The other end40 of the vessel 35 is ligated by sutures 41, and its collaterals 42 areligated by sutures 43. This causes the vessel 35 to define an enclosedchamber. Within the interior of the vessel 35 is a straight rod 44,which extends the major part of the length of the vessel. The rod 44 ismade of a suitable inert material, such as glass or a plastic such aspolyolefin, and is of a constant outside diameter. The diameter of therod 44 is less than that the vessel 35 assumes when it is under itsnormal physiologic pressure. The rod, however, serves to keep the vessel35 straight under all conditions, this being the natural configurationfor the vessel illustrated.

The manifold 37 is connected through a line 45 to an elevated reservoirof tanning fluid or other source of tanning fluid under pressure withinthe physiologic range. The internally applied tanning fluid inflates thevessel 35 so that during its period of fixation it assumes generally thenormal diameter of a pressurized vessel. The tanning fluid in the tank39 is applied to the exterior of the vessel 30 simultaneously to theinternal pressurization with tanning fluid from the manifold 37. Whentreated in this manner, the vessel 35 has an improved shape, greatertensile strength and more uniformity of fixation with a greaterpenetration of the fixative than if conventional fixing procedures arefollowed.

The rod within the vessel need not be straight, but may be shaped toother contours to correspond to a desired overall configuration for thevessel. As shown in FIG. 8, the rod 46 is U-shaped, maintaining thatcontour for a vessel 47 which in its natural state has a differentshape. Again, the end 48 of the vessel 47 is ligated as are itscollaterals 49. The vessel is immersed in the tanning fluid 33 andattached to the manifold stem 36, as before. Pressure then is applied tothe interior of the vessel during its period of fixation. When thetanning operation is complete, the vessel will retain substantially theU-shaped contour of the rod 46. This enables specially shaped naturalvessels to be produced to suit particular requirements. The U-shapedvessel, for example, can be used as a shunt between vein and arteryduring kidney dialysis.

Instead of a rod within the vessel, a tube may be placed around thevessel to perform a similar function of maintaining it in a desiredconfiguration. In FIG. 9 there is shown a U-shaped tube 50 of constantdiameter surrounding a vessel 51, which has a natural shape differingfrom that of the tube. The tube 50 has a greater diameter than that ofthe vessel 51 before its interior is pressurized, as shown. However,pressurization of the vessel 51 will expand it to approach the lateraldimension of the tube 50. The tube 50 keeps the vessel 51 in the propershape throughout the tanning process.

Other configurations of rod or tube may be devised to accommodatevessels to be fixed either in their natural shapes or in differentshapes. Bifurcations, trifurcations and the like are possible utilizinga tube as the guiding element.

The foregoing detailed description is to be clearly understood as givenby way of illustration and example only, the spirit and scope of thisinvention being limited solely by the appended claims.

We claim:
 1. The method of preparing .Iadd.a .Iaddend.natural heartvalve for implantation .Iadd.so that said valve will have improvedtensile strength, will have and retain a generally regular contour withthe cusps thereof closed as in diastole, and will be in substantiallyits natural configuration, so that said valve will remain competent fora prolonged period upon implantation, .Iaddend.comprising the stepsof.Iadd.excising a heart valve from a donor heart, .Iaddend.applying atanning fluid under pressure in the physiologic range to the downstreamend of .[.a natural.]. .Iadd.said .Iaddend.heart valve .Iadd.so excised.Iaddend.so as to cause said valve to assume .Iadd.a generally regularcontour with the cusps thereof coapted and closed as in diastole so thatsaid valve is in .Iaddend.substantially its natural configuration, andsimultaneously applying a tanning fluid to the upstream end of saidvalve .Iadd.and to substantially the entire exterior surface of saidvalve .Iaddend.at a pressure less than that at said downstreamend,thereby to cause said valve substantially to maintain saidconfiguration during .Iadd.and after .Iaddend.fixation of the tissuethereof .Iadd.so that said valve can remain competent for a prolongedperiod of use upon implantation. .Iaddend.
 2. The method of preparing.[.a.]. .Iadd.the .Iaddend.natural heart valve .Iadd.of an animal.Iaddend.for implantation .Iadd.in a patient so that said valve willhave improved tensile strength, will have and retain a generally regularcontour with the cusps thereof closed as in diastole, and will be insubstantially its natural configuration, so that said valve will remaincompetent for a prolonged period of use upon implantation.Iaddend.comprising the steps of.Iadd.excising a heart valve from ananimal heart, .Iaddend.applying a tanning fluid under pressure withinthe physiologic range to the downstream end of .[.a natural.]..Iadd.said .Iaddend.heart valve .Iadd.so excised .Iaddend.so as to causesaid valve to assume .Iadd.a generally regular contour with the cuspsthereof coapted and closed as in diastole so that said valve is in.Iaddend.substantially its natural configuration, applying said tanningfluid to the upstream end of said valve while said tanning fluid underpressure is so applied to said valve at the downstream end thereof sothat said valve is at a higher pressure .Iadd.from said tanning fluid.Iaddend.at said downstream end than at said upstream end, .[.and.].maintaining said tanning fluid so applied to said heart valve for a timesufficient to cause said valve to become fixed so as to substantiallymaintain said configuration .Iadd.and to have improved tensile strength,whereby said valve can remain competent for a prolonged period of useupon implantation, and thereafter removing said valve so fixed from saidtanning fluid and mounting said valve on a stent for subsequentimplantation. .Iaddend.
 3. The method as recited in claim 2 in whichsaid pressure is substantially within the range of from about 80 toabout 120 mm Hg.
 4. The method as recited in claim 2 in which saidtanning fluid is a 4% formaldehyde solution, and in which said tanningfluid is so applied to said valve for around 72 hours.
 5. The method asrecited in claim 2 in which said tanning fluid is a 0.2% glutaraldehydesolution, and in which said tanning fluid is so applied to said valvefor around 72 hours.
 6. The method as recited in claim 2 in which saidtanning fluid under pressure is applied to said valve by maintaining aquantity of said tanning fluid so as to have a predetermined maximumheight with respect to said valve, and connecting said quantity oftanning fluid to said valve so that said quantity of tanning fluidproduces a pressure head applied to said valve.
 7. The method ofpreparing a natural heart valve for implantation .Iadd.so that saidvalve will have improved tensile strength, will have and retain agenerally regular contour with the cusps thereof closed as in diastole,and will be in substantially its natural configuration, so that saidvalve will remain competent for a prolonged period upon implantation,.Iaddend.comprising the steps of.Iadd.excising from a donor heart a unitthat includes a heart valve and its ascending aorta, then.Iaddend.inserting .Iadd.into said ascending aorta above said heartvalve .Iaddend.a member having an aperture therethrough.Iadd.,.Iaddend..[.into the ascending aorta of a unit that includes a naturalheart valve and its ascending aorta,.]. attaching said aorta to saidmember so that said unit and said member define a chamber .Iadd.closedat one end by the cusps of said heart valve .Iaddend.and said apertureprovides access to the interior of said chamber at the downstream end ofsaid valve, ligating the arteries of said unit so as to close saidchamber, introducing a tanning fluid which is pressurized to within thephysiologic range of pressure for said valve through said aperture intosaid chamber so as to inflate said valve and cause said valve to assume.Iadd.a generally regular contour with the cusps thereof coapted andclosed as in diastole so that said valve is .Iaddend.substantially itsnatural configuration, .Iadd.with said tanning fluid being retained bysaid cusps of said heart valve, .Iaddend. applying such tanning fluid tothe exterior of said unit .Iadd.so that said tanning fluid engagessubstantially the entire exterior surface of said heart valve.Iaddend.while said pressurized tanning fluid is in said chamber with agreater fluid pressure existing in said chamber than on said exterior,.[.and.]. maintaining said pressurized tanning fluid and said tanningfluid so applied to the exterior of said unit for a time sufficient tocause the tissue of said valve to become substantially fixed,thereby tocause said valve to substantially maintain said configuration .Iadd.andto have improved tensile strength, and thereafter removing said valve sofixed from said tanning fluid and mounting said valve on a stent inpreparation for implantation. .Iaddend.
 8. The method as recited inclaim 7 in which for introducing said pressurized fluid into saidchamber a source of said tanning fluid is maintained at a predeterminedheight relative to said unit, and in which a conduit is extended fromsaid source of said tanning fluid to said chamber to cause said tanningfluid at said source to provide a predetermined pressure head.
 9. Themethod as recited in claim 8 in which said predetermined height isselected so as to provide a pressure head of around 80 mm Hg. .[.10. Themethod of preparing for implantation natural tissues in a form in whicha portion thereof is subjected to pressure within the physiologic rangewhen implanted and which assumes a predetermined configuration as aresult of such pressure comprising the steps ofapplying a tanning fluidto said portion of said tissues,said tanning fluid so applied beingunder pressure in the physiologic range so as to cause said tissues toassume substantially said predetermined configuration, andsimultaneously applying a tanning fluid to remaining parts of saidtissues at a pressure less than that of said portion of saidtissues,thereby to cause said tissues to assume said configurationduring fixation of said tissues..]. .[.11. The method as recited inclaim 10 in which, for so applying said tanning fluid to said portion ofsaid tissues with said tanning fluid being under pressure within thephysiologic range, a source of said tanning fluid under pressure isprovided, and a conduit is extended from said source to said portion ofsaid tissues, for thereby so applying said tanning fluid to said portionof said tissues..]. .[.12. The method as recited in claim 11 in which,for said source of said tanning fluid under pressure, a quantity of saidtanning fluid is provided at a predetermined height relative to saidportion of said tissues..]. .[.13. The method of preparing a vessel forimplantation comprising the steps of subjecting said vessel to a bath oftanning fluid so as to fix said vessel, and simultaneously engaging saidvessel with a guide member of predetermined contour for causing saidvessel to assume substantially said predetermined contour upon fixationthereof, said predetermined contour being different from the contour ofsaid vessel in its natural state..]. .[.14. The method of preparing forimplantation natural tissues in a form in which a portion thereof issubjected to pressure within the physiologic range when implanted andwhich assumes a predetermined configuration as a result of such pressurecomprising the steps of applying a tanning fluid to said portion of saidtissues, said tanning fluid so applied being under pressure within thephysiologic range so as to cause said tissues to assume substantiallysaid predetermined configuration, and applying a tanning fluid toremaining parts of said tissues while said tanning fluid under pressureis so applied to said portion of said tissues,so that said tissuesexperience a higher pressure at said portion thereof than at saidremaining parts thereof..]. .[.15. The method as recited in claim 14including the step of engaging said tissues with a guide member ofpredetermined contour while said tanning fluid under pressure within thephysiologic range is so applied to said portion of said tissues forcausing said tissues to assume substantially said predeterminedcontour..]. .[.16. The method as recited in claim 15 in which saidtissues constitute a vessel..]. .[.17. The method as recited in claim 16in which said vessel in its natural state has substantially saidpredetermined contour..]. .[.18. The method as recited in claim 16 inwhich said vessel in its natural state has a contour different from saidpredetermined contour..]. .[.19. The method as recited in claim 28 inwhich said predetermined contour is substantially U-shaped..]. .[.20.The method as recited in claim 16 in which, for said engaging of saidvessel with a guide member, an elongated element having substantiallysaid predetermined contour, and a lateral dimension less than thatassumed by said vessel when subjected to pressure within the physiologicrange, is inserted into said vessel for thereby maintaining said vesselsubstantially in said predetermined contour..]. .[.21. The method asrecited in claim 16 in which, for said engaging of said vessel with aguide member, said vessel is placed within a tubular element havingsubstantially said predetermined contour and an interior lateraldimension approximately that assumed by said vessel when subjected topressure within the physiologic range, for thereby maintaining saidvessel substantially in said predetermined contour..]. .[.22. The methodas recited in claim 16 in which, for applying said pressure to saidvessel, the end and any collaterals thereof are ligated, and saidtanning fluid under pressure within said physiologic range is introducedinto the interior of said vessel..]. .[.23. The method as recited inclaim 22 in which, for introducing said tanning fluid under pressurewithin the physiologic range into said vessel, a source of said tanningfluid is maintained at a predetermined hight relative to said vessel,and a conduit is extended from said source of said tanning fluid to saidvessel to cause said tanning fluid at said source to provide apredetermined pressure head..].
 24. A .Iadd.stent-mounted.Iaddend.natural heart valve for implantation having a generally regularcontour, natural shape and size, coaptation of the cusps thereof andrelatively high tensile strength prepared by the steps of.Iadd.excisinga heart valve from a donor heart, .Iaddend.applying a tanning fluidunder pressure in the physiologic range to the downstream end of .[.anatural.]. .Iadd.said .Iaddend.heart valve .Iadd.so excised .Iaddend.soas to cause said valve to assume substantially its naturalconfiguration, and simultaneously applying a tanning fluid to theupstream end of said valve .Iadd.and to substantially the entireexterior surface of said valve .Iaddend.at a pressure less than that atsaid downstream end,thereby to cause said valve substantially tomaintain said configuration during fixation of the tissue thereof.
 25. A.Iadd.stent-mounted .Iaddend.natural heart valve for implantation havinga generally regular contour, natural shape and size, coaptation of thecusps thereof and relatively high tensile strength prepared by the stepsof.Iadd.excising a heart valve from an animal heart, .Iaddend.applying atanning fluid under pressure within the physiologic range to thedownstream end of .[.a natural.]. .Iadd.said .Iaddend.heart valve.Iadd.so excised .Iaddend.so as to cause said valve to assumesubstantially its natural configuration, applying said tanning fluid tothe upstream end of said valve .Iadd.so that said tanning fluid engagessubstantially the entire exterior surface of said valve .Iaddend.whilesaid tanning fluid under pressure is so applied to said valve at thedownstream end thereof so that said valve is at a higher pressure.Iadd.from said tanning fluid .Iaddend.at said downstream end than atsaid upstream end, and maintaining said tanning fluid so applied to saidheart valve for a time sufficient to cause said valve to become fixed soas to substantially maintain said configuration.
 26. The heart valve asrecited in claim 25 in which said pressure is substantially within therange of from about 80 to about 120 mm Hg.
 27. The heart valve asrecited in claim 25 in which said tanning fluid is a 4% formaldehydesolution, and in which said tanning fluid is so applied to said valvefor around 72 hours.
 28. The heart valve as recited in claim 25 in whichsaid tanning fluid is a 0.2% glutaraldehyde solution, and in which saidtanning fluid is so applied to said valve for around 72 hours.
 29. Theheart valve as recited in claim 25 in which said tanning fluid underpressure is applied to said valve by maintaining a quantity of saidtanning fluid so as to have a predetermined maximum height with respectto said valve, and connecting said quantity of tanning fluid to saidvalve so that said quantity of tanning fluid produces a pressure headapplied to said valve.
 30. A .Iadd.stent-mounted .Iaddend.natural heartvalve for implantation having a generally regular contour, natural shapeand size, coaptation of the cusps thereof and relatively high tensilestrength prepared by the steps of.Iadd.excising from a donor heart aunit that includes a heart valve and its ascending aorta, then.Iaddend.inserting .Iadd.into said ascending aorta above said heartvalve .Iaddend.a member having an aperture therethrough.Iadd., .Iaddend..[.into the ascending aorta of a unit that includes a natural heartvalve and its ascending aorta,.]. attaching said aorta to said member sothat said unit and said member define a chamber .Iadd.closed at one endby the cusps of said heart valve .Iaddend.and said aperture providesaccess to the interior of said chamber at the downstream end of saidvalve, ligating the arteries of said unit so as to close said chamber,introducing a tanning fluid which is pressurized to within thephysiologic range of pressure for said valve through said aperture intosaid chamber so as to inflate said valve and cause said valve to assumesubstantially its natural configuration, .Iadd.with said tanning fluidbeing retained by said cusps of said heart valve, .Iaddend. applyingsuch tanning fluid to the exterior of said unit .Iadd.so that saidtanning fluid engages substantially the entire exterior surface of saidheart valve .Iaddend.while said pressurized tanning fluid is in saidchamber with a greater fluid pressure existing in said chamber than onsaid exterior, and maintaining said pressurized tanning fluid and saidtanning fluid so applied to the exterior of said unit for a timesufficient to cause the tissue of said valve to become substantiallyfixed,thereby to cause said valve to substantially maintain saidconfiguration. . The heart valve as recited in claim 30 in which forintroducing said pressurized fluid into said chamber a source of saidtanning fluid is maintained at a predetermined height relative to saidunit, and in which a conduit is extended from said source of saidtanning fluid to said chamber to cause said tanning fluid at said sourceto provide a predetermined pressure head.
 32. The heart valve as recitedin claim 31 in which said predetermined height is selected so as toprovide a pressure head of around 80 mm Hg. .[.33. Natural tissues forimplantation and in a form in which a portion thereof is subjected topressure within the physiologic range when implanted and which assumes apredetermined configuration as a result of such pressure, said tissueshaving full and uniform fixation and a relatively high tensile strength,and prepared by the steps ofapplying a tanning fluid to said portion ofsaid tissues,said tanning fluid so applied being under pressure in thephysiologic range so as to cause said tissues to assume substantiallysaid predetermined configuration, and simultaneously applying a tanningfluid to remaining parts of said tissues at a pressure less than that ofsaid portion of said tissues,thereby to cause said tissues to assumesaid configuration during fixation of said tissues..]. .[.34. Thetissues as recited in claim 33 in which for so applying said tanningfluid to said portion of said tissues with said tanning fluid beingunder pressure within the physiologic range, a source of said tanningfluid under pressure is provided, and a conduit is extended from saidsource to said portion of said tissues, for thereby so applying saidtanning fluid to said portion of said tissues..]. .[.35. The tissues asrecited in claim 34 in which for said source of said tanning fluid underpressure, a quantity of said tanning fluid is provided at apredetermined height relative to said portion of said tissues..]. .[.36.A vessel for implantation having a contour different from the contourthereof in its natural state prepared by the steps ofsubjecting saidvessel to a bath of tanning fluid so as to fix said vessel, andsimultaneously engaging said vessel with a guide member of predeterminedcontour for causing said vessel to assume substantially saidpredetermined contour upon fixation thereof,said predetermined contourbeing different from the contour of said vessel in its natural state..]..[.37. Natural tissues for implantation and in a form in which a portionthereof is subjected to pressure within the physiologic range whenimplanted and which assumes a predetermined configuration as a result ofsuch pressure, said tissues having full and uniform fixation and arelatively high tensile strength, and prepared by the steps of applyinga tanning fluid to said portion of said tissues,said tanning fluid soapplied being under pressure within the physiologic range so as to causesaid tissues to assume substantially said predetermined configuration,and applying a tanning fluid to remaining parts of said tissues whilesaid tanning fluid under pressure is so applied to said portion of saidtissues,so that said tissues experience a higher pressure at saidportion thereof than at said remaining parts thereof..]. .[.38. Thetissues as recited in claim 37 in which said preparation thereofincludes the step of engaging said tissues with a guide member ofpredetermined contour while said tanning fluid under pressure within thephysiologic range is so applied to said portion of said tissues forcausing said tissues to assume substantially said predeterminedcontour..]. .[.39. The tissues as recited in claim 38 in which saidtissues constitute a vessel..]. .[.40. The vessel as recited in claim 39in which said vessel in its natural state has substantially saidpredetermined contour..]. .[.41. The vessel as recited in claim 39 inwhich said vessel in its natural state has a contour different from saidpredetermined contour..]. .[.42. The vessel as recited in claim 41 inwhich said predetermined contour is substantially U-shaped..]. .[.43.The vessel as recited in claim 39 in which for said engaging of saidvessel with a guide member, an elongated element having substantiallysaid predetermined contour, and a lateral dimension less than thatassumed by said vessel when subjected to pressure within the physiologicrange, is inserted into said vessel for thereby maintaining said vesselsubstantially in said predetermined contour..]. .[.44. The vessel asrecited in claim 39 in which for said engaging of said vessel with aguide member, said vessel is placed within a tubular element havingsubstantially said predetermined contour and an interior lateraldimension approximately that assumed by said vessel when subjected topressure within the physiologic range, for thereby maintaining saidvessel substantially in said predetermined contour..]. .[.45. The vesselas recited in claim 39 in which for applying said pressure to saidvessel, the end and any collaterals thereof are ligated, and saidtanning fluid under pressure within said physiologic range is introducedinto the interior of said vessel..]. .[.46. The vessel as recited inclaim 39 in which for introducing said tanning fluid under pressurewithin the physiologic range into said vessel, a source of said tanningfluid is maintained at a predetermined height relative to said vessel,and a conduit is extended from said source of said tanning fluid to saidvessel to cause said tanning fluid at said source to provide apredetermined pressure head..]. .Iadd.
 47. The method as recited inclaim 2 in which, for so applying said tanning fluid to said upstreamend of said valve, said valve is submersed in a bath of said tanningfluid. .Iaddend..Iadd.
 48. The method as recited in claim 7 in which,for so applying said tanning fluid to the exterior of said unit, saidunit is positioned in a bath of said tanning fluid so that said tanningfluid of said bath engages substantially the entire outer surface ofsaid valve. .Iaddend. .Iadd.
 49. The method as recited in claim 7 inwhich, for so applying said tanning fluid to the exterior of said unit,said unit is positioned in a tank containing said tanning fluid so thatsaid tanning fluid of said tank engages substantially the entire outersurface of said heart valve, and in which for so introducing saidpressurized tanning fluid into said chambera reservoir containing saidtanning fluid is maintained at a predetermined height above said unit,and a conduit is extended from said reservoir to said aperture of saidmember to cause said tanning fluid of said reservoir to provide apredetermined pressure head within said chamber. .Iaddend. .Iadd. 50.The method of simultaneously preparing a plurality of natural heartvalves for implantation so that said valves will have improved tensilestrength, will have and retain generally regular contours with theircusps closed as in diastole, and will be substantially in their naturalconfigurations, so that said valves will remain competent for prolongedperiods of use upon implantation comprising the steps of excising from aplurality of donor hearts a plurality of units each of which includes aheart valve and its ascending aorta, then inserting into each of saidascending aortas a member having an aperture therethrough, attachingsaid aorta of each of said units to the one of said members insertedtherein so that said units and said members define chambers, ligatingthe arteries of each of said units so as to close said chambers,attaching said members to a manifold, connecting a source of pressurizedtanning fluid to said manifold so that said pressurized tanning fluid isintroduced simultaneously into said chambers through said apertures ofsaid members and exerts in said chambers a pressure which is within thephysiologic range of pressure for said valves,thereby to inflate saidvalves and cause them to assume generally regular contours with theircusps coapted and closed as in diastole so that said valves are insubstantially their natural configuration with said tanning fluid beingretained in said chambers by the cusps of said heart valves, positioningsaid manifold adjacent a tank containing a quantity of said tanningfluid so that said valves are submerged in said tanning fluid in saidtank and said tanning fluid engages substantially the entire outersurfaces of said heart valves, while said source of pressurized tanningfluid is so attached to said manifold and exerts a greater fluidpressure in said chambers than on said outer surfaces of said valves,and maintaining said source of pressurized tanning fluid so connected tosaid manifold and said manifold so positioned adjacent said tank for atime sufficient to cause the tissues of said valves to becomesubstantially fixed,thereby to cause said valves to substantiallymaintain said configurations and to have improved tensile strength..Iaddend. .Iadd.
 51. The method as claimed in claim 50 including thesteps of inspecting said valves while said source of pressurized tanningfluid is so connected to said manifold to detect loss of saidpressurized tanning fluid through said valves, and discarding those ofsaid valves through which there is an excessive loss of said pressurizedtanning fluid. .Iaddend. .Iadd.
 52. In the method of replacing adiseased heart valve in a human patient with a natural tissue valvetaken from an animal or a human wherein the natural tissue valve isfixed prior to implantation by exposure to a tanning fluid andthereafter mounted on a stent or affixed directly to the annulus of theheart of the patient, the improvement comprisingapplying a tanning fluidunder pressure in the physiologic range to the downstream end of saidnatural tissue valve so as to cause said valve to assume substantiallyits natural configuration, and simultaneously applying a tanning fluidto the upstream end of said valve and to substantially the entireexterior surface of said valve at a pressure less than that at saiddownstream end,thereby to cause said valve substantially to maintainsaid configuration during fixation of the tissue thereof..Iaddend..Iadd.
 53. In the method of replacing a diseased heart valve ina human patient with a natural tissue valve taken from an animal or ahuman wherein the natural tissue valve is fixed prior to implantation byexposure to a tanning fluid and thereafter mounted on a stent or affixeddirectly to the annulus of the heart of the patient, the improvementcomprising applying a tanning fluid under pressure within thephysiologic range to the downstream end of said natural tissue valve soas to cause said valve to assume substantially its naturalconfiguration, applying said tanning fluid to the upstream end of saidvalve while said tanning fluid under pressure is so applied to saidvalve at the downstream end thereof so that said valve is at a higherpressure from said tanning fluid at said downstream end than at saidupstream end, and maintaining said tanning fluid so applied to saidvalve for a time sufficient to cause said valve to become fixed so as tosubstantially maintain said configuration. .Iaddend..Iadd.
 54. Themethod as recited in claim 53 in which said pressure is substantiallywithin the range of from about 80 to about 120 mm Hg. .Iaddend. .Iadd.55. The method as recited in claim 53 in which said tanning fluid underpressure is applied to said valve by maintaining a quantity of saidtanning fluid so as to have a predetermined maximum height with respectto said valve, and connecting said quantity of tanning fluid to saidvalve so that said quantity of tanning fluid produces a pressure headapplied to said valve. .Iaddend..Iadd.
 56. The method as recited inclaims 1, 2, 7, 53 or 54 in which said tanning fluid is a glutaraldehydesolution. .Iaddend..Iadd.
 57. In the method of replacing a diseasedheart valve in a human patient with a natural tissue valve taken from ananimal or a human wherein the natural tissue valve is fixed prior toimplantation by exposure to a tanning fluid and thereafter mounted on astent or affixed directly to the annulus of the heart of the patient,the improvement comprising excising from a donor heart a unit thatincludes a heart valve and its ascending aorta, then inserting into saidascending aorta above said heart valve a member having an aperturetherethrough, attaching said aorta to said member so that said unit andsaid member define a chamber closed at one end by the cusps of saidheart valve and said apertures provides access to the interior of saidchamber at the downstream end of said valve, ligating the arteries ofsaid unit so as to close said chamber, introducing a glutaraldehydesolution which is pressurized to substantially within the range of 80 mmHg to 120 mm Hg pressure through said aperture into said chamber so asto inflate said valve and cause said valve to assume substantially itsnatural configuration, with said glutaraldehyde solution being retainedby said cusps of said heart valve, applying a glutaraldehyde solution tothe exterior of said unit so that said glutaraldehyde solution engagessubstantially the entire exterior surface of said heart valve while saidpressurized glutaraldehyde solution is in said chamber, with a greaterfluid pressure existing in said chamber than on said exterior, andmaintaining said pressurized glutaraldehyde solution in said chamber andsaid glutaraldehyde solution so applied to the exterior of said unit fora time sufficient to cause the tissue of said valve to becomesubstantially fixed,thereby to cause said valve to substantiallymaintain said configuration. .Iaddend..Iadd.
 58. The method as recitedin claim 57 in which for introducing said glutaraldehyde solution intosaid chamber a source of said glutaraldehyde solution is maintained at apredetermined height relative to said unit, and in which a conduit isextended from said source of said glutaraldehyde solution to saidchamber to cause said glutaraldehyde solution at said source to providea predetermined pressure head. .Iaddend..Iadd.
 59. The method as recitedin claim 58 in which said predetermined height is selected so as toprovide a pressure head of around 80 mm Hg. .Iaddend.